A large and growing body of psychoneuroimmunology research demonstrates that psychological stress is an important moderator of immune system functioning. Recent studies suggest, however, that it is not the presence of a stressor per se but rather individual difference in appraisals of, and responses to, the stressor that leads to changes in the immune system. Those individual differences are likely a function of distinct personality traits such as neuroticism and conscientiousness - heritable characteristics that are strongly related to exposure to life events as well as health outcomes. Herpes simplex virus (HSV) infection is a principle focus of psychoneuroimmunology research because HSV infections are ubiquitous in humans and the determinants of the clinical and virological severity are unknown. The primary outcome measures in psychoneuroimmunology studies of HSV are typically clinical symptoms or antibody titers. But these measures do not necessarily reflect increases in shedding and thus increased risk of HSV transmission. We have developed an objective method to quantify the virologic severity of HSV infections on mucosal surfaces that is more sensitive than measuring symptoms and more specific than measuring antibody titers. In this project we will combine assessment of personality and stress-related psychological variables with the most sensitive and clinically relevant outcome measure in HSV research for a twin study that will allow us to control for the genetics of both the study participants and variability in virus genotype. We will thus compare HSV shedding rates for disease-concordant same-sex monozygotic (MZ) and dizygotic (DZ) twin pairs while assessing daily stress appraisals and weekly reports of specific stressors and related appraisals, along with psychological traits including neuroticism, conscientiousness, and optimism. Using this twin design will allow us to assess biological and psychosocial aspects of stress and HSV shedding, while controlling for genetic variability and common familial exposures and experiences. The Specific Aims are to 1) assess the influence of stressors and stress appraisals on HSV shedding rates;2) determine the relationship between measures of personality and HSV shedding rates;and 3) assess the joint influence of stressors, stress appraisals, and measures of personality on HSV shedding rates. PUBLIC HEALTH RELEVANCE: There is a growing body of research that links personality traits, stress, and stress attributions to outbreaks of herpes simplex virus type 1 (HSV-1) among those who are already HSV-positive. However, a great deal remains to be discovered about how personality and stress affect the immune system. In this study, we will examine the relationships among personality, stress, and HSV-1 in twins to better elucidate how the person, the virus, and the environment interact.